"Man, know thyself" was the challenge of ancient Greek philosophers and it has been the goal of mankind since.

Thousands of years later, neuroscientists are trying to decipher how the human brain constructs our sense of self, with mixed results. Pretty pictures mapped to activity can only tell us so much. But if self-awareness is defined as being aware of oneself, including traits, feelings, and behaviors, there are three brain regions critical for self-awareness, they say: the insular cortex, the anterior cingulate cortex and the medial prefrontal cortex.

Or not. A research team now says self-awareness is more a product of a diffuse patchwork of pathways in the brain and not confined to specific areas. They say that because they got a rare opportunity to study a person with extensive brain damage to all three regions believed critical for self-awareness. The person, a 57-year-old, college-educated man known as "Patient R," passed all standard tests of self-awareness. He also displayed repeated self-recognition, both when looking in the mirror and when identifying himself in unaltered photographs taken during all periods of his life.

In other words, as philosophers also noted, the whole is greater than the sum of its parts. But looking for parts is the extent of what can be done today and so the authors of the new paper contend the brainstem, thalamus, and posteromedial cortices also play roles in self-awareness.

Patient R, who has severe damage to three regions long considered integral to self-awareness in humans (from left to right: the insular cortex, anterior cingulate cortex, and the medial prefrontal cortex). Based on the scans, researchers believe self-awareness is a product of a diffuse patchwork of pathways in the brain rather than confined to specific areas. T1-weighted MRI scans of R's lesion. a) Sagittal images highlighting damage to the insular cortex, (b) sagittal images highlighting damage to the ACC, and (c) coronal images highlighting damage to the mPFC. All three structures are extensively damaged, bilaterally, in R's brain.Credit: Department of Neurology, University of Iowa. Link: doi:10.1371/journal.pone.0038413.g001

The researchers observed that Patient R's behaviors and communication often reflected depth and self-insight. First author Dr. Carissa Philippi conducted a detailed self-awareness interview with Patient R and said he had a deep capacity for introspection, one of humans' most evolved features of self-awareness.

"During the interview, I asked him how he would describe himself to somebody," said Philippi, a post-doctoral researcher at the University of Wisconsin-Madison. "He said, 'I am just a normal person with a bad memory.'"

Patient R also demonstrated self-agency, meaning the ability to perceive that an action is the consequence of one's own intention. When rating himself on personality measures collected over the course of a year, Patient R showed a stable ability to think about and perceive himself. However, his brain damage also affected his temporal lobes, causing severe amnesia that has disrupted his ability to update new memories into his "autobiographical self." Beyond this disruption, all other features of R's self-awareness remained fundamentally intact.

"Most people who meet R for the first time have no idea that anything is wrong with him," noted Rudrauf. "They see a normal-looking middle-aged man who walks, talks, listens, and acts no differently than the average person. According to previous research, this man should be a zombie. But as we have shown, he is certainly not one. Once you've had the chance to meet him, you immediately recognize that he is self-aware."

Patient R is a member of the University of Iowa's Iowa Neurological Patient Registry, which was established in 1982 and has more than 500 active members with various forms of damage to one or more regions in the brain. The researchers had begun questioning the insular cortex's role in self-awareness in a 2009 study that showed that Patient R was able to feel his own heartbeat, a process termed "interoceptive awareness."

Theys estimate that Patient R has ten percent of tissue remaining in his insula and one percent of tissue remaining in his anterior cingulate cortex. Some had seized upon the presence of tissue to question whether those regions were in fact being used for self-awareness. But neuroimaging results presented in the current study reveal that Patient R's remaining tissue is highly abnormal and largely disconnected from the rest of the brain.

"Here, we have a patient who is missing all the areas in the brain that are typically thought to be needed for self-awareness yet he remains self-aware," added co-corresponding author Justin Feinstein, who earned his doctorate at the University of Iowa in February. "Clearly, neuroscience is only beginning to understand how the human brain can generate a phenomenon as complex as self-awareness."